Expression of the AID protein in normal and neoplastic B cells Journal Article


Authors: Pasqualucci, L.; Guglielmino, R.; Houldsworth, J.; Mohr, J.; Aoufouchi, S.; Polakiewicz, R.
Article Title: Expression of the AID protein in normal and neoplastic B cells
Abstract: Somatic hypermutation (SHM) targets primarily the immunoglobulin variable region (IgV) genes in germinal center (GC) B cells, thereby allowing antibody affinity maturation. A malfunction of SHM, termed aberrant somatic hypermutation (ASHM), was found in about 50% of diffuse large B-cell lymphomas (DLBCLs), leading to mutations in the 5' sequences of multiple genes, including oncogenes. Although the SHM mechanism is largely unknown, it was shown to require the activation-induced cytidine deaminase (AID) gene. AID mRNA is expressed in GC B cells and GC-derived lymphomas, but the pattern of expression of the AID protein is not known. Using 2 specific antibodies, here we show that the AID protein can be detected in GC centroblasts and their transformed counterpart (Burkitt lymphoma) but not in pre-GC B cells and post-GC neoplasms, including B-cell chronic lymphocytic leukemia and multiple myeloma. DLBCLs displayed variable levels of AID expression, which did not correlate with IgV ongoing hypermutation, ASHM, or disease subtype. Finally, both in normal and malignant B cells the AID protein appeared predominantly localized in the cytoplasm. These results indicate that the AID protein is specifically expressed in normal and transformed GC B cells; nonetheless, its predominantly cytoplasmic localization suggests that additional mechanisms may regulate its function and may be altered during lymphomagenesis. (C) 2004 by The American Society of Hematology.
Keywords: c-myc; recombination; single-stranded-dna; chronic lymphocytic-leukemia; messenger-rna; class-switch; antibody diversification; induced cytidine deaminase; heavy-chain locus; aberrant somatic hypermutation; germinal center reaction
Journal Title: Blood
Volume: 104
Issue: 10
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2004-11-15
Start Page: 3318
End Page: 3325
Language: English
ACCESSION: WOS:000225094100054
DOI: 10.1182/blood-2004-04-1558
PROVIDER: wos
PUBMED: 15304391
Notes: Article -- Source: Wos
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